Coronary artery disease (CAD) is the leading cause of mortality and morbidity in the developed world. CAD is widely treated by implantation of stents (e.g., balloon stents) in the coronary artery. In-stent restenosis, the recurrence of constriction of an artery following efforts to dilate it, is a common side effect, affecting 20% to 40% of patients by 6 months after percutaneous coronary interventions (PCI), with neointimal hyperplasia being the primary cause.
Rapamycin (sirolimus), an antibiotic that inhibits cell migration and proliferation, is effective in reducing restenosis. However, prolonged exposure of smooth muscle cells to rapamycin results in the development of resistance to the drug (Luo et al., 1996, Mol. Cell. Biol. 16: 6744-6751).